Organic acids are widely used in food, pharmaceutical and textile industries, and are widely recognized to be one of the key chemical building blocks in biorefining. Organic acids are also of interest for the production of polymers which are used as biodegradable plastics.
A number of microbes are capable of producing organic acids by aerobic and anaerobic fermentation processes. Lactobacillus species are currently used extensively in industry for starch-based lactic acid production. The majority of these species lack the ability to ferment pentose sugars such as xylose and arabinose. Although Lactobacillus pentosus, Lactobacillus brevis and Lactococcus lactis are able to ferment pentoses to lactic acid, pentoses are metabolized using the phosphoketolase pathway which is inefficient for lactic acid production. Indeed, in the phosphoketolase pathway, xylulose 5-phosphate is cleaved to glyceraldehyde 3-phosphate and acetyl-phosphate. With this pathway, the maximum theoretical yield of lactic acid is limited to one per pentose (0.6 g lactic acid per g xylose) due to the loss of two carbons to acetic acid.
In most platform host organisms such as E. coli, production of organic acids at high titers is either inefficient or toxic. The production of organic acids such as lactic acid at neutral pH typically results in the production of Ca-lactate, which has to be converted into lactic acid by the addition of sulphuric acid, resulting in the formation of CaSO4 (gypsum) as by product. To produce lactic acid directly, the fermentation must be executed at low pH (preferably at least one unit lower than the pKa value of lactic acid, 3.85). Lactic acid however is toxic to microorganisms, as in its protonated form it acts as an uncoupler that destroys the membrane potential. Thus, while quite some micro-organisms may be tolerant to low pH only a limited number of organisms are suitable for organic acid production in that they are tolerant to organic acids at reduced pH.
An important drawback to bacterial fermentation is the cost. As many bacteria are unable to synthesize some of the amino acids or proteins they need for growing and for metabolizing sugars efficiently, bacteria often must be fed a somewhat complex package of nutrients, increasing the direct expense to operate the fermentation. In addition, the increased complexity of the broth makes it more difficult to recover the fermentation product in reasonably pure form, so increased operating and capital costs are incurred to recover the product. Also, the use of corn as the feedstock competes directly with the food and feed.
Accordingly, there remains a need for improved biocatalysts for lactic acid fermentation processes.